1. Field of the Invention
The present invention relates to a method for producing optically active lactone compounds. More specifically, the invention relates to a method for producing optically active lactone compounds by Baeyer-Villiger oxidation of cyclic ketone compounds using salen cobalt complexes possessing a cis-xcex2 structure as a catalyst. Such optically active lactone compounds can be used for the synthesis of medicines and agrochemicals. Further, both S isomers and R isomers can be synthesized by choosing the catalyst.
2. Related Art Statement
Asymmetric Baeyer-Villiger oxidation is an important reaction in the organic synthetic chemistry. Still, these is no general method for achieving sufficient enantioselectivity in the oxidation. Baeyer-Villiger oxidation starts with nucleophilic attach of an oxidant to a carboxyl group, followed by the migration of the carbonyl-substitutent (R3 or R4) to the vicinal oxygen atom to give a lactone (or esters). Lewis acid accelerates both the nuclceophic addition and the migration through its coordination to the carbonyl group and the leaving group (Xxe2x80x2), respectively. The reaction formula is shown below. 
Bolm and co-workers reported enantiomer-differentiating Bayer-Villiger oxidation of racemic 2-substituted cycloalkanones using a combination of molecular oxygen and aldehyde (Mukaiyama condition) in the presence of bis(oxazolinyl-phenolato)copper (II) complex as a catalyst (Bolm C., Schlingloff G. and Weichhardt K., Angew. Chem. Int. Ed. Engl. 1994, 33, 1848-1849). Enantioselective Baeyer-Villiger oxidation using chiral platinum complexes as catalysts were also reported (Gusso A., Baccin C., Pinna F., and Strukul G., Organometallics, 1994, 13, 3442-3451). Thereafter, asymmetric Baeyer-Villiger oxidations using various optically active metal complexes as catalysts have been investigated, and high enatioselectivity has been realized for the reactions of some specific substrates.
However, the maximum enantioselectivity in the reported asymmetric Baeyer-Villiger oxidation of prochiral ketones, particularly, prochiral 3-substituted cyclobutanone compounds by using optically active metal complexes as catalyst was 47%ee (until August, 2001) (Lopp M., Paju A., Kanger T., and Pehk T., Tetrahedron Lett., 1996, 37, 7583-7586, Bolm C., Schlingloff G., and Bienewald E, J. Mol. Cat. A; Chem., 1997, 117, 347-350, Bolm C., and Beckmann O., Chirality, 2000, 12, 523-525, Shinohara T., Fujioka S., and Kotsuki, H., Heterocycles, 2001, 55, 237-241).
Therefore, it is an object of the present invention to provide a method for producing lactone compounds at an optically high purity by asymmetric Baeyer-Villiger oxidation of prochiral ketones.
Having made strenuous investigations to solve the above-mentioned problems, the inventors discovered that lactone compounds of optically high purities could be produced by the Baeyer-Villiger oxidation of cyclic ketone compounds with specific oxidants in the presence of cobalt(salen) complexes of cis-xcex2 structure as catalyst. The present invention was accomplished based on this discovery.
(1) That is, the present invention relates to a method for producing an optically active lactone compound by Baeyer-Villiger oxidation of a cyclic ketone compound with at least one kind of oxidants selected from the group consisting of hydrogen peroxide and urine-hydrogen peroxide adduct (UHP) in the presence of a cobalt(salen) complex possessing cis-xcex2 structure expressed by the following formula (I) or (II) as a catalyst. 
in which X and Y independently denote H, t-butyl group or an electron-withdrawing substituting group and W is a halogen element. 
in which X and Y independently denote H, t-butyl group or an electron-withdrawing group and Zxe2x88x92 is a monovalent non-coordinating anion.
The followings are preferred embodiments of the lactone-producing method of the present invention.
(2) X and Y in the cobalt(salen) complex of the formula (I) independently denote t-butyl group, F, Cl, Br, I or a nitro group.
(3) X and Y in the cobalt(salen) complex of the formula (I) denote t-butyl group and nitro group, respectively.
(4) W in the cobalt(salen) complex of the formula (I) denotes iodine.
(5) X and Y in the cobalt(salen) complex of the formula (II) independently denote F, Cl, Br or I.
(6) X and Y in the cobalt(salen) complex of the formula (II) denote F.
(7) Zxe2x88x92 in the cobalt(salen) complex of the formula (II) denotes non-coordinating anion such as SbF6xe2x88x92.
(8) The cyclic ketone compound is represented by any one of the following formulae (III), (IV) and (V). 
in which R1 is a substituted or non-substituted C1-C20 alkyl group or a substituted or non-substituted C6-C15 aryl group. 
in which R2 is a substituted or non-substituted C1-C20 alkyl group or a substituted or non-substituted C6-C15 aryl group. 
(9) The cyclic ketone compound is represented by the formula (III).
(10) The cyclic ketone compound is 3-phenylcyclobutanone, 3-(p-chlorophenyl)cyclobutanone, 3-(p-methoxyphenyl)cyclobutanone or 3-octyl cyclobutanone.
(11) The cyclic ketone compound is represented by the formula (V).
(12) The lactone compound is represented by any one of the following formulae (VI), (VII) and (VIII). 
in which R1 is a substituted or non-substituted C1-C20 alkyl group or a substituted or on-substituted C6-C15 aryl group. 
in which R2 is a substituted or non-substituted C1-C20 alkyl group or a substituted or non-substituted C6-C15 aryl group. 
(13) The lactone compound is represented by the formula (VI).
(14) The lactone compound is xcex2-phenyl-xcex3-butylolactone, xcex2-(p-chlorophenyl)-xcex3-butylolactone, xcex2-(p-methoxyphenyl)-xcex3-butylolactone or xcex2-octyl-xcex3-butylolactone.
(15) The lactone compound is represented by the formula (VIII).
(16) The lactone compound has an optical purity of not less than 47% ee.
(17) The lactone compound-producing method further uses at least one kind of polar solvents.
(18) The polar solvent is any one selected from acetonitrile, ethyl acetate, diethyl ether, tetrahydrofuran (THF) and a C1-C3 alcohol.
(19) The Baeyer-Villiger oxidation is effected in a temperature range of xe2x88x9220xc2x0 C. to 25xc2x0 C.
Any combinations of (2) to (19) are also preferred embodiments of the lactone-producing method according to the present invention, so long as no discrepancy occurs.
The present invention also relates to a catalyst to be used in the above-mentioned methods, that is,
(20) the invention relates to a cobalt(salen) complex having a cis-xcex2 structure represented by the following formula (I) or (II). 
in which in which X and Y independently denote H, t-butyl group or an electron-withdrawing group and W is a halogen element. 
in which X and Y independently denote H, t-butyl group or an electron-withdrawing group and Zxe2x88x92 is a monovalent non-coordinating anion.
The followings are preferred embodiments of the complexes of the present invention.
(21) X and Y in the cobalt(salen) complex of the formula (I) independently denote t-butyl group, F, Cl, Br, I or nitro group.
(22) X and Y in the cobalt(salen) complex of the formula (I) denote t-butyl group and nitro group, respectively.
(23) W in the cobalt(salen) complex of the formula (I) denotes iodine.
(24) X and Y in the cobalt(salen) complex of the formula (II) independently denote F, Cl, Br or I.
(25) X and Y in the cobalt(salen) complex of the formula (II) denote F.
(25) Zxe2x88x92 in the cobalt(salen) complex of the formula (II) denotes non-coordinating anion such as SbF6xe2x88x92.
Any combinations of (21) to (26) are also preferred embodiments of the catalyst of the present invention, so long as no discrepancy occurs.
These and other objects, features and advantages of the invention will be apparent from reading of the following detailed description of the invention when taken with the understanding that some variations, changes or variations could be easily made by the skilled person in the art to which the invention pertains.
In the following, the present invention will be explained in more detail. The Baeyer-Villiger oxidation utilized in the producing method according to the present invention, which is also called the Baeyer-Villiger reaction or the Baeyer-Villigar rearrangement, is a reaction in which an ester is produced by oxidation of a ketone with peroxide. The lactone is obtained by subjecting the cyclic ketone compound to this reaction. Further, the optically active lactone compound is obtained by subjecting the prochiral cyclic ketone compound to the above reaction.
The Baeyer-Villiger oxidation consists of two steps: (i) nucleophilic attack of an oxidant to a carbonyl compound to give Criegee adduct and (ii) rearrangement of the adduct to give an ester (or lactone). Therefore, the stereochemistry of the Baeyer-Villiger oxidation is influenced by two factors: (i) the face-selectivity in the addition of the oxidant and (ii) the enantiotopos-selectivity in the rearrangement. According to the present invention, the Baeyer-Villiger oxidation of the prochiral cyclic ketone compounds with use of the specific metal catalysts and specific oxidants as mentioned later improves the face-selectivity and the enantiotopos-selectivity, so that the optically active lactone compounds are obtained.
The cobalt(salen) complex possessing the cis-xcex2 structure to be used as the catalyst in the present invention is expressed by either one of the following formulae (I) and (II). 
In the formula (I), X and Y independently denote H, t-butyl group or an electron-withdrawing group. As the electron-withdrawing group, halogen elements such as F, Cl, Br and I as well as a nitro group may be recited. As X and Y in the formula (I), t-butyl group, F, Cl, Br, I and nitro group are preferred. It is particularly preferable that X is t-butyl group and Y is nitro group. W is a halogen element, and Br and I are recited as the halogen element. I is preferred, because I weakly bonds to cobalt and easily dissociates therefrom in the reaction system.
In the formula (II), X and Y independently denote H, t-butyl group or an electron-withdrawing group. As the electron-withdrawing group, the same as referred to in the explanation of X and Y in the formula (I) are recited. As X and Y in the formula (II), F, Cl, Br and I are preferred. It is particularly preferable that both X and Y are F. Zxe2x88x92 is a monovalent non-coordinating anion. For example, SbF6xe2x88x92 and PF6xe2x88x92 may be reicted, and SbF6xe2x88x92 is preferred. Since Zxe2x88x92 is the monovalent non-coordinating anion, the complex represented by the formula (II) is cationic.
The cobalt(salen) complex represented by the formula (II) is obtained by reacting the cobalt(salen) complex of the formula (I) with silver hexafluoroantimonate or the like, for example. Therefore, the cobalt(salen) complex of the formula (I) is more easily synthesized as compared with that of the formula (II). The cobalt(salen) complex of the formula (I) is more easily handled than that of the formula (II). Therefore, the cobalt(salen) complex of the formula (I) is more preferable from the standpoint of the production cost and the handling easiness of the complex.
The loading amount of the catalyst according to the present invention is preferably in a range of 1 to 10 mol %, more preferably 4 to 6 mol % relative to 1 mol of the cyclic ketone as the substrate.
The cationic cobalt(salen) complex of the formula (II) has two vacant coordinating sites adjacent to each other above the central metal, and these coordinating sites are available for coordination of the substrate and the oxidant. On the other hand, in the cobalt(salen) complex of the formula (I), W coordinating to the central metal is easily dissociated in the reaction system, so that the cobalt ion can possess two vacant coordinating sites adjacent to each other, and these coordinating sites are available for the coordination of the substrate and the oxidant.
Therefore, when the cobalt(salen) complex of either the formula (I) or (II) is used for the asymmetric Baeyer-Villiger oxidation, the oxygen atom of the carbonyl group of the substrate and the oxygen atom of the oxidant simultaneously on stepwise coordinate to the central metal and the Baeyer-Villiger oxidation occurs in the coordination sphere of the cobalt ion. Accordingly, the face-selectivity in nucleophilic attack of the oxygen atom of the oxidant to the carbon atom of the carbonyl group of the substrate and enantiotopos-selectivity in the rearrangement of the Criegee adduct resulting from the nucleophilic attack are achieved. Therefore, the cobalt(salen) complex used in the producing method of the present invention is required to have two vacant coordinating sites adjacent to each other above the metal on which the desired Baeyer-Villiger oxidation proceeds.
The cyclic ketone compound to be used in the present invention is a prochiral cyclic ketone compound, which forms a chiral carbon in the Baeyer-Villiger oxidation. For example, the compounds represented by the following formulae (III), (IV) and (V) are recited. In this application, the prochiral cyclic ketone compounds mean the cyclic ketones that form a chiral carbon through the reaction. 
in which R1 is a substituted or non-substituted C1-C20 alkyl group or a substituted or non-substituted C6-C15 aryl group. 
in which R2 is a substituted or non-substituted C1-C20 alkyl group or a substituted or non-substituted C6-C15 aryl group. 
As the alkyl group in R1 of the formula (III), methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, 2-ethylhexyl, nonyl, decyl, undecyl, dodecyl, tridecyl, isotridecyl, myristyl, palmityl, stearyl, eicocyl, docosyl, etc. may be recited.
As the aryl group in R1 of the formula (III), phenyl, tolyl, xylyl, cumyl, mesityl, ethylphenyl, propylphenyl, butylphenyl, pentylphenyl, hexylphenyl, heptylphenyl, octylphenyl, nonylphenyl, xcex1-naphthyl, xcex2-naphthyl, etc. may be recited.
The above alkyl group and aryl group may be substituted by a halogen, a C1-C4 alkoxy group or the like.
As the alkyl group and the aryl group in R2 of the formula (IV), those recited as the alkyl group and the aryl group in R1 of the above formula (III) may be also recited. These alkyl groups and aryl groups may be substituted by a halogen, a C1-C4 alkoxy group or the like.
The oxidant to be used in the present invention is hydrogen peroxide or an urea-hydrogen peroxide adduct (UHP). Each of these oxidants coordinates to the central metal of the cobalt(salen) complex, attacks the carbonyl group as the substrate and produces the chelated Criegee adduct. Another possibility is that the oxidant attacks the carbonyl compound and coordinates to the central metal to give the chelated Criegee adduct. On the other hand, if t-butyl hydroxyperoxide (TBHP) or metha-chloroperbenzoic acid (m-CPBA) is used as the oxidant, the oxidant attacks the carbonyl compounds to produce a non-chelated Criegee adduct an intermediate. In this case, since the oxygen atom of the carbonyl group as the substrate and the oxygen atom of the oxidant do not simultaneously coordinate to the central metal, the enantoiselectivity is extremely deteriorated. The use amount of the above oxidant is preferably 1 to 2 equivalents, more preferably 1.2 to 1.3 equivalent relative to the cyclic ketone as the substrate.
The optically active lactone compound as the product of the present invention is produced by subjecting the above-mentioned prochiral cyclic ketone compound to the asymmetric Baeyer-Villiger oxidation. Since the enantiotopos-selective rearrangement of the chelated Criegee adduct is high in the producing method of the present invention as mentioned above, the optically active lactone compound is obtained. The optically active lactone compounds produced form the cyclic ketones by the present invention have formulae (VI), (VII), (VIII), etc. and are recited. 
in which R1 has the same meaning as mentioned above. 
in which R2 has the same meaning as mentioned above. 
The optical purity to be used as an index for the purity of the optical isomer of the present invention is expressed by the following formula.
[Mathematical formula]      Optical    ⁢          xe2x80x83        ⁢    purity    ⁢          xe2x80x83        ⁢          (              %        ⁢        ee            )        =                                          [            α            ]                    D                xc3x97        100                              [          α          ]                          D          ⁢                      xe2x80x83                    ⁢          max                      =                                                      (                              R                -                S                            )                        xc3x97            100                                R            +            S                          ⁢                  xe2x80x83                ⁢        or        ⁢                  xe2x80x83                ⁢                                            (                              S                -                R                            )                        xc3x97            100                                R            +            S                              =                                                  Enantiometric              ⁢                              xe2x80x83                            ⁢              excess                                                                          percentage              ⁢                              xe2x80x83                            ⁢                              (                                  %                  ⁢                  ee                                )                                                        
in which [xcex1]D is a specific optical rotation degree of a sample, [xcex1]Dmax is a specific optical rotation degree of an optically pure substance, R is a ratio of an R isomer in the sample, and S is a ratio of an S isomer in the sample. Therefore, the optical purity is equal to the excess ratio of the enantiomers. If the ratio of the R isomer is equal to that of the S isomer, that is, if the sample is a racemic product, the optical purity is 0% ee. The optical purity (excess ratio of the enantiomers) of the product can be measured by a high performance liquid chromatography (HPLC) using an optically active column.
The producing method of the present invention is usually effected in a solvent. As the solvent, halogenated alkanes such as dichloromethane, ether compounds such as tetrahydrofuran (THF) and diethyl ether, nitrile compounds such as acetonitrile, esterified compounds such as ethyl acetate, C1-C3 alcohol compounds such as methanol, ethanol and isopropanol, aliphatic hydrocarbons such as hexane, aromatic hydrocarbons such as benzene and toluene, etc. may be recited. Among them, polar solvents such as the halogenated alkane, the ether compound, the nitrile compound, the ester compound and the alcohol compound are preferred from the standpoint of enhancing the reaction speed and the excess percentage of the enantiomers. Acetonitrile, ethyl acetate, tetrahydrofuran, diethyl ether and the C1-C3 alcohol compounds are particularly preferred. The use amount of the solvent is preferably 1-10 ml, more preferably 4-5 ml relative to 1 mmol of the cyclic ketone as the substrate.
The producing method of the present invention can be effected at room temperature. The reaction is preferably effected at not more than room temperature, for example, 0xc2x0 C. to xe2x88x9220xc2x0 C., because the optical purity of the product increases due to the enhanced excess percentage of the enantiomers, although the yield of the product decreases in the reaction at such a temperature.
According to the present invention, the optically active lactone compound can be produced by stirring a mixed solution of the cyclic ketone compound, the oxidant, the solvent and the catalyst. Stirring is not limited to a particular way so long as the uniformity of the mixed solution can be ensured. A known stirring method can be used. The reaction time is not particularly limited, and appropriately selected depending upon the reaction temperature. It is preferable that the higher the reaction temperature, the shorter is the reaction time, whereas the lower the reaction temperature, the longer is the reaction time.